Immunology of advancing disease among minorities with Multiple Sclerosis

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PROJECT SUMMARY Greater disease severity and a more rapid disease progression is observed among US minority populations such as African Americans (AA) and Hispanics (Latinx) with Multiple Sclerosis (MS) compared to whites with MS. Despite these observations, very little data is available regarding the biological underpinnings resulting in this increased risk of unequivocal advancing disease among minorities with MS even though the incidence of MS disease is growing among minority populations. Further, there are concerns that AA and Latinx with MS are refractory to first-line therapies, which increases the concern that the poor outcomes reported reflect substandard care and treatment. Our long term goal is to facilitate prevention of neurological deficits in minority patients with MS by identifying the mechanism(s) of CNS inflammation contributing to intensified progression and severity of disease. Others have shown that minorities with MS display higher IgG index and synthesis rate, oligoclonal band positivity and an inverse correlation of IgG index with gray matter atrophy. These data support a pronounced role for B cells and their antibody products in the pathobiology of MS in minority populations. Our central hypothesis is that the underlying mechanism of unequivocal advancing disease among minorities with MS involves expansion of plasmablasts producing antibodies and/or inflammatory products that cause neuronal toxicity independent of genetic (i.e. ancestral) predispositions. These studies will provide novel mechanistic insights into the role of neuron-reactive plasmablasts in CNS inflammatory events associated with intensified progression and severity of disease in minorities with MS. Our findings will also support future studies to develop diagnostic and predictive tools that inform patient response to treatment and inform clinical course such as relapse of MS or progression to MS in minority populations.